Canani R, Costanzo M, Bedogni G, Amoroso A, Cosenza L, Scala C, Granata V, Nocerino R. - - J Allergy Clin Immunol 2017.

Extensively hydrolysed casein formula containing L. rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow’s milk allergy: 3-year randomized controlled trial

BACKGROUND: Children with cow’s milk allergy (CMA) have an increased risk of developing other allergic manifestations (AMs).

OBJECTIVE: We performed a parallel-arm randomized controlled trial (RCT) to test whether the administration of an extensively hydrolysed casein formula (EHCF) containing the probiotic L. rhamnosus GG (LGG) can reduce the occurrence of other AMs in CMA children.

METHODS: Children with IgE-mediated CMA were randomly allocated to EHCF or EHCF LGG groups and followed for 36 months. The main outcome was the occurrence of at least one AM (eczema, urticaria, asthma and rhinoconjunctivitis). The secondary outcome was tolerance acquisition, defined as the negativization of a double-blind food challenge at 12 months, 24 months and 36 months. AMs were diagnosed according to standardized criteria. Tolerance acquisition was evaluated every 12 months.

RESULTS: A total of 220 children (147 males, 67%) with a median (IQR) age of 5.0 (3.0-8.0) months were randomized and 110 children were placed in the EHCF group and 110 children were placed in the EHC +LGG group. In the complete case analysis, the absolute risk difference (ARD) for the occurrence of at least one AM over 36 months was -0.23 [95%CI -0.36 to -0.10, p<0.001] and the ARD for the acquisition of cow’s milk tolerance was 0.20 (95%CI 0.05 to 0.35, p<0.01) at 12 months, 0.24 (95%CI 0.08 to 0.41, p<0.01) at 24 months and 0.27 (95%CI 0.11 to 0.43, p<0.001) at 36 months. In the sensitivity analysis, the effect size of the main outcome was virtually unchanged when the occurrence of AM was assigned to all 27 missing children.

CONCLUSIONS: EHCF+LGG reduces the incidence of other AMs and hastens the development of oral tolerance in children with IgE-mediated CMA.

Keywords: Eczema; urticaria; asthma; rhinoconjunctivitis; atopic march; food allergy; gut microbiota; probiotics